Matrix metalloproteinases (MMPs) belong to a family of extracellular enzymes involved in forming and remodeling the extracellular matrix. These enzymes contain a conserved catalytic domain in which a zinc atom is coordinated by three histidine residues. Over 20 members of this family are known, organized into a number of groups including collagenases, gelatinases, stromelysins, matrilysins, enamelysins and membrane MMPs.
MMP2 and MMP9 belong to the gelatinase group of matrix metalloproteinases. Besides containing signal peptide, propeptide, catalytic, zinc-binding and heamopexin-like domains common to most MMPs, the gelatinases also contain a plurality of fibronectin-like domains and an O-glycosylated domain.
MMPs are involved in a number of diseases. Inhibitors of MMPs have not been entirely satisfactory, in part related to specificity and efficacy. Thus, there is a need for specific and effective MMP inhibitors. Treatment of cancers and inflammatory and autoimmune diseases, such as colorectal cancer, IBD (including Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis), rheumatoid arthritis (RA), and others, have not been entirely satisfactory. Thus, there is a need for treatments effective in such diseases, particularly for subjects in which available therapeutics have been ineffective.